Hypertension and heart failure are major health problems worldwide. Patients with hypertensive heart disease and heart failure develop cardiovascular fibrosis that significantly reduces heart function. Typically, fibrosis develops when the body's natural wound-healing process goes awry. Under normal conditions of wound healing, specialized cells known as fibroblasts become activated by transforming to myofibroblast. The myofibroblasts then undergo proliferation causing increased synthesis of collagen protein in the extracellular matrix composed predominantly of type I collagen and to a lesser extent type III collagen (normal wound healing process). What is initially an adaptive process, perhaps meant to enhance tensile strength, can progress to maladaptive (pathologic) conditions when the “healing” process persists with the development of diffuse and heterogeneous myocardial fibrosis characterized by a matrix made of increased collagen deposits and myofibroblast numbers. Thus, rationally designed antifibrotic therapies are highly desirable. The use of agents to block the renin-angiotensinaldosterone and sympathetic nervous systems has been shown to inhibit (and sometimes even reverse) cardiovascular fibrosis and to improve the clinical course of patients with cardiac dysfunction. However, drugs aiming at direct inhibition or reduction of cardiovascular fibrosis are not yet available, largely because the underlying basis of cardiovascular fibrosis is unclear.